Large trans-ethnic meta-analysis identifies AKR1C4 as a novel gene associated with age at menarche.

STUDY QUESTION: Does the expansion of genome-wide association studies (GWAS) to a broader range of ancestries improve the ability to identify and generalise variants associated with age at menarche (AAM) in European populations to a wider range of world populations? SUMMARY ANSWER: By including women with diverse and predominantly non-European ancestry in a large-scale meta-analysis of AAM with half of the women being of African ancestry, we identified a new locus associated with AAM in African-ancestry participants, and generalised loci from GWAS of European ancestry individuals. WHAT IS KNOWN ALREADY: AAM is a highly polygenic puberty trait associated with various diseases later in life. Both AAM and diseases associated with puberty timing vary by race or ethnicity. The majority of GWAS of AAM have been performed in European ancestry women. STUDY DESIGN, SIZE, DURATION: We analysed a total of 38 546 women who did not have predominantly European ancestry backgrounds: 25 149 women from seven studies from the ReproGen Consortium and 13 397 women from the UK Biobank. In addition, we used an independent sample of 5148 African-ancestry women from the Southern Community Cohort Study (SCCS) for replication. PARTICIPANTS/MATERIALS, SETTING, METHODS: Each AAM GWAS was performed by study and ancestry or ethnic group using linear regression models adjusted for birth year and study-specific covariates. ReproGen and UK Biobank results were meta-analysed using an inverse variance-weighted average method. A trans-ethnic meta-analysis was also carried out to assess heterogeneity due to different ancestry. MAIN RESULTS AND THE ROLE OF CHANCE: We observed consistent direction and effect sizes between our meta-analysis and the largest GWAS conducted in European or Asian ancestry women. We validated four AAM loci (1p31, 6q16, 6q22 and 9q31) with common genetic variants at P < 5 × 10-7. We detected one new association (10p15) at P < 5 × 10-8 with a low-frequency genetic variant lying in AKR1C4, which was replicated in an independent sample. This gene belongs to a family of enzymes that regulate the metabolism of steroid hormones and have been implicated in the pathophysiology of uterine diseases. The genetic variant in the new locus is more frequent in African-ancestry participants, and has a very low frequency in Asian or European-ancestry individuals. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Extreme AAM (<9 years or >18 years) were excluded from analysis. Women may not fully recall their AAM as most of the studies were conducted many years later. Further studies in women with diverse and predominantly non-European ancestry are needed to confirm and extend these findings, but the availability of such replication samples is limited. WIDER IMPLICATIONS OF THE FINDINGS: Expanding association studies to a broader range of ancestries or ethnicities may improve the identification of new genetic variants associated with complex diseases or traits and the generalisation of variants from European-ancestry studies to a wider range of world populations. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by CHARGE Consortium grant R01HL105756-07: Gene Discovery For CVD and Aging Phenotypes and by the NIH grant U24AG051129 awarded by the National Institute on Aging (NIA). The authors have no conflict of interest to declare.

Building better bones in childhood: a randomized controlled study to test the efficacy of a dietary intervention program to increase calcium intake.

BACKGROUND/OBJECTIVES: Many children do not consume the recommended daily allowance of calcium. Inadequate calcium intake in childhood may limit bone accrual. The objective of this study was to determine if a behavioral modification and nutritional education (BM-NE) intervention improved dietary calcium intake and bone accrual in children. SUBJECTS/METHODS: 139 (86 female) healthy children, 7-10 years of age, were enrolled in this randomized controlled trial conducted over 36 months. Participants randomized to the BM-NE intervention attended five sessions over a 6-week period designed to increase calcium intake to 1500 mg/day. Participants randomized to the usual care (UC) group received a single nutritional counseling session. The Calcium Counts Food Frequency Questionnaire was used to assess calcium intake; dual energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD) and bone mineral content (BMC). Longitudinal mixed effects models were used to assess for an effect of the intervention on calcium intake, BMC and aBMD. RESULTS: BM-NE participants had greater increases in calcium intake that persisted for 12 months following the intervention compared with UC. The intervention had no effect on BMC or aBMD accrual. Secondary analyses found a negative association between calcium intake and adiposity such that greater calcium intake was associated with lesser gains in body mass index and fat mass index. CONCLUSIONS: A family-centered BM-NE intervention program in healthy children was successful in increasing calcium intake for up to 12 months but had no effect on bone accrual. A beneficial relationship between calcium intake and adiposity was observed and warrants future study.

Effect of high-dose cholecalciferol (vitamin D3) on bone and body composition in children and young adults with HIV infection: a randomized, double-blind, placebo-controlled trial.

It is unknown whether vitamin D supplementation positively impacts body composition and bone outcomes in children and young adults with HIV. This RCT found that despite increasing 25(OH)D concentrations, high dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection. INTRODUCTION: The objective of this paper was to determine the impact of high-dose daily cholecalciferol (vitamin D3) supplementation on body composition and bone density, structure, and strength in children and young adults with perinatally acquired (PHIV) or behaviorally acquired (BHIV) HIV infection. METHODS: Participants were randomized to receive vitamin D3 supplementation (7000 IU/day) or placebo for 12 months. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, dual energy X-ray absorptiometry (DXA) of the whole body and lumbar spine, and peripheral quantitative computed tomography (pQCT) of tibia sites were acquired at 0, 6, and 12 months. DXA and pQCT outcomes were expressed as sex- and population-ancestry specific Z-scores relative to age and adjusted for height or tibia length, as appropriate. RESULTS: Fifty-eight participants (5.0 to 24.9 years) received vitamin D3 supplements (n = 30) or placebo (n = 28). At enrollment, groups were similar in age, sex, population ancestry, growth status, serum 25(OH)D concentrations, body composition, and size-adjusted bone measures. Median 25(OH)D concentrations were similar (17.3 ng/mL in the vitamin D3 supplementation group vs 15.6 ng/mL in the placebo group), and both groups had mild bone deficits. At 12 months, 25(OH)D rose significantly in the vitamin D supplementation group but not in the placebo group (26.4 vs 14.8 ng/mL, respectively, p < 0.008). After adjusting for population ancestry, sex, antiretroviral therapy use, and season, there were no significant treatment group differences in bone or body composition outcomes. CONCLUSIONS: Despite increasing 25(OH)D concentrations, 12 months of high-dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection.

The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations.

Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one's genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.

Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays.

UNLABELLED: A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D. INTRODUCTION: This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations. METHODS: DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21-80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D. RESULTS: Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r s = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (-0.34, p < 0.001) versus free/bioavailable 25(OH)D (-0.18/-0.24 depending on DBP assay, p ≤ 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites. CONCLUSIONS: The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.

Bone structure of adolescent swimmers; a peripheral quantitative computed tomography (pQCT) study.

OBJECTIVES: The aims of the present study were: (1) to characterize vBMD, bone structure and strength with peripheral quantitative computerized tomography (pQCT) in adolescent swimmers and compare it to normo-active controls (CG); and (2) to evaluate the possible interaction that weight-bearing sports might have on swimmers bone. DESIGN: Cross-sectional. METHODS: The non-dominant radius and tibia of 79 (32 females) swimmers and 49 (22 females) CG (both 11-18 years old) were evaluated at proximal and distal sites with a pQCT scanner. Values of total, trabecular and cortical volumetric bone mineral density (vBMD) were obtained from each scan. Cortical thickness, endosteal and periosteal circumferences were also measured and bone strength indexes were calculated. Analyses of covariance were used to compare variables between groups adjusting for age, tanner stage and bone length. Three different analyses were performed according to present and past sport participation in addition to swimming in order to determine differences among swimmers who had performed or were performing other sports (OTHER-SP) (10 females/17 males) and swimmers who had not performed other sports (NO-OTHER-SP) (22 females/22 males). Both of these groups were compared to each other and to a CG (22 females/27 males). RESULTS: No differences were found between swimmers and CG for bone strength indexes, structure or vBMD (independently of the compared sample). CONCLUSIONS: These results indicate that swimmers present similar bone strength and structure than CG who did not present high physical activity levels.

The impact of vitamin D3 supplementation on muscle function among HIV-infected children and young adults: a randomized controlled trial.

OBJECTIVES: We tested the hypothesis that daily vitD3 supplementation increases neuromuscular motor skills, jump power, jump energy, muscular force, and muscular strength. METHODS: This was a secondary analysis of a randomized controlled trial of 12-months of oral 7,000 IU/day vitD3 supplementation or placebo among 56 persons living with HIV aged 9-25 years. Neuromuscular motor skills were quantified using the Bruininks-Oseretsky Test of Motor Proficiency. Power was quantified using peak jump power, and energy was quantified using peak jump height. Muscular force was quantified using isometric ankle plantar- and dorsiflexion, isokinetic knee flexion and extension. Muscular strength was quantified using isometric handgrip strength. RESULTS: After 12-months, serum 25-hydroxyvitamin D [25(OH)D] was higher with supplementation versus placebo (ß=12.1 ng/mL; P<0.001). In intention-to-treat analyses, supplementation improved neuromuscular motor skills versus placebo (ß=1.14; P=0.041). We observed no effect of supplementation on jump power, jump energy, muscular force, or muscular strength outcomes versus placebo. CONCLUSIONS: Among HIV-infected children and young adults supplementation with daily high-dose vitD3 increased concentration of serum 25(OH)D and improved neuromuscular motor skills versus placebo.

Use of proton pump inhibitors is associated with fractures in young adults: a population-based study.

UNLABELLED: Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture. INTRODUCTION: Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. METHODS: We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ≥ 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. RESULTS: We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and 1.39 (95% CI 1.26 to 1.53) among young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <0.001). CONCLUSIONS: PPI use was associated with fracture in young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.

Anthropometric models of bone mineral content and areal bone mineral density based on the bone mineral density in childhood study.

UNLABELLED: New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. INTRODUCTION: Previous descriptions of children's bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. METHODS: We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's bone mineral values. By balancing high adjusted R(2) values with clinical needs, two models are examined. RESULTS: At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below -2, from the standard sex, race, and age model. CONCLUSIONS: If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters.

Changes in trabecular bone density in incident pediatric Crohn's disease: a comparison of imaging methods.

UNLABELLED: This study of changes in dual energy x-ray absorptiometry (DXA) spine BMD following diagnosis and treatment for childhood Crohn's disease demonstrated that changes in conventional posteroanterior BMD results were confounded by impaired growth, and suggested that lateral spine measurements and strategies to estimate volumetric BMD were more sensitive to disease and treatment effects. INTRODUCTION: We previously reported significant increases in peripheral quantitative CT (pQCT) measures of trabecular volumetric bone mineral density (vBMD) following diagnosis and treatment of pediatric Crohn's disease (CD). The objective of this study was to compare pQCT trabecular vBMD and three DXA measures of spine BMD in this cohort: (1) conventional posteroanterior BMD (PA-BMD), (2) PA-BMD adjusted for height Z (PA-BMDHtZ), and (3) width-adjusted volumetric BMD (WA-BMD) estimated from PA and lateral scans. METHODS: Spine DXA [lumbar (L1-4) for posteroanterior and L3 for lateral] and tibia pQCT scans were obtained in 65 CD subjects (ages 7-18 years) at diagnosis and 12 months later. BMD results were converted to sex, race, and age-specific Z-scores based on reference data in >650 children (ages 5-21 years). Multivariable linear regression models identified factors associated with BMD Z-scores. RESULTS: At CD diagnosis, all BMD Z-scores were lower compared with the reference children (all p values <0.01). The pQCT vBMD Z-scores (-1.46 ± 1.30) were lower compared with DXA PA-BMD (-0.75 ± 0.98), PA-BMDHtZ (-0.53 ± 0.87), and WA-BMD (-0.61 ± 1.10) among CD participants. Only PA-BMD Z-scores were correlated with height Z-scores at baseline (R = 0.47, p < 0.0001). pQCT and WA-BMD Z-scores increased significantly over 12 months to -1.04 ± 1.26 and -0.20 ± 1.14, respectively. Changes in all four BMD Z-scores were positively associated with changes in height Z-scores (p < 0.05). Glucocorticoid doses were inversely associated with changes in WA-BMD (p < 0.01) only. CONCLUSIONS: Conventional and height Z-score-adjusted PA DXA methods did not demonstrate the significant increases in trabecular vBMD noted on pQCT and WA-BMD scans. WA-BMD captured glucocorticoid effects, potentially due to isolation of the vertebral body on the lateral projection. Future studies are needed to identify the BMD measure that provides greatest fracture discrimination in CD.

Changes in DXA and quantitative CT measures of musculoskeletal outcomes following pediatric renal transplantation.

This prospective study evaluated changes in dual energy X-ray absorptiometry (DXA) whole body bone mineral content (WB-BMC) and spine areal bone mineral density (spine-BMD), and tibia quantitative computed tomography (QCT) trabecular and cortical volumetric BMD and cortical area in 56 children over 12 months following renal transplantation. At transplant, spine-BMD Z-scores were greater in younger recipients (<13 years), versus 898 reference participants (p < 0.001). In multivariate models, greater decreases in spine-BMD Z-scores were associated with greater glucocorticoid dose (p < 0.001) and declines in parathyroid hormone levels (p = 0.008). Changes in DXA spine-BMD and QCT trabecular BMD were correlated (r = 0.47, p < 0.01). At 12 months, spine-BMD Z-scores remained elevated in younger recipients, but did not differ in older recipients (≥ 13) and reference participants. Baseline WB-BMC Z-scores were significantly lower than reference participants (p = 0.02). Greater glucocorticoid doses were associated with declines in WB-BMC Z-scores (p < 0.001) while greater linear growth was associated with gains in WB-BMC Z-scores (p = 0.01). Changes in WB-BMC Z-scores were associated with changes in tibia cortical area Z-scores (r = 0.52, p < 0.001), but not changes in cortical BMD Z-scores. Despite resolution of muscle deficits, WB-BMC Z-scores at 12 months remained significantly reduced. These data suggest that spine and WB DXA provides insight into trabecular and cortical outcomes following pediatric renal transplantation.

Resting energy expenditure and adiposity accretion among children with Down syndrome: a 3-year prospective study.

BACKGROUND: Children with Down syndrome (DS) have a higher prevalence of obesity than other children. Whether this increased risk for obesity is due to a lower resting energy expenditure (REE) is controversial. Our study assessed whether (1) the REE of children with DS adjusted for fat-free mass (FFM) was lower than that of sibling controls, and (2) the changes in fat mass (FM) over 3 years were associated with FFM-adjusted baseline REE. METHODS: This study used cross-sectional and prospective cohort designs. Four annual measurement visits were conducted with 28 children with DS and 35 sibling controls aged 3-10 years. REE and serum thyroxine (T4) were measured at baseline. Anthropometry, skinfold thickness measures, and, in a subsample, dual-energy x-ray absorptiometry (DXA) were used at each visit to calculate FM. RESULTS: Children with DS had significantly lower REE adjusted for FFM (-78 kcal/day, 95% CI: -133 to -27, P=0.003). The difference remained significant after adjustment for FM, sex and African ancestry (-49 kcal/day, 95% CI: -94 to -4, P=0.03). In the longitudinal analysis, the baseline REE adjusted for baseline FFM was not predictive of FM accretion over time (P=0.8). CONCLUSION: Children with DS have lower REE than sibling controls, but REE was not associated with changes in FM over time. The results suggest that the lower REE of children with DS does not explain their increased risk for obesity.

Fitting of bone mineral density with consideration of anthropometric parameters.

UNLABELLED: A new model describing normal values of bone mineral density in children has been evaluated, which includes not only the traditional parameters of age, gender, and race, but also weight, height, percent body fat, and sexual maturity. This model may constitute a better comparative norm for a specific child with given anthropometric values. INTRODUCTION: Previous descriptions of children's bone mineral density (BMD) by age have focused on segmenting diverse populations by race and gender without adjusting for anthropometric variables or have included the effects of anthropometric variables over a relatively homogeneous population. METHODS: Multivariate semi-metric smoothing (MS(2)) provides a way to describe a diverse population using a model that includes multiple effects and their interactions while producing a result that can be smoothed with respect to age in order to provide connected percentiles. We applied MS(2) to spine BMD data from the Bone Mineral Density in Childhood Study to evaluate which of gender, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's BMD values. By balancing high adjusted R (2) values and low mean square errors with clinical needs, a model using age, gender, race, weight, and percent body fat is proposed and examined. RESULTS: This model provides narrower distributions and slight shifts of BMD values compared to the traditional model, which includes only age, gender, and race. Thus, the proposed model might constitute a better comparative standard for a specific child with given anthropometric values and should be less dependent on the anthropometric characteristics of the cohort used to devise the model. CONCLUSIONS: The inclusion of multiple explanatory variables in the model, while creating smooth output curves, makes the MS(2) method attractive in modeling practically sized data sets. The clinical use of this model by the bone research community has yet to be fully established.

Special report on the 2007 adult and pediatric Position Development Conferences of the International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20-21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Body composition and metabolic factors in obese children and adolescents.

OBJECTIVE: Body composition is associated with metablic factors in adults; however, data are limited regarding obese children. This study was undertaken to assess body composition, regional fat distribution, and metabolic factors in obese 6-18-y-old children and adolescents. DESIGN: Cross-sectional assessment. SUBJECTS: Thirty-six obese children and adolescents, (mean+/-s.e.m.) age 11.8+/-0.5 y, BMI 34.1+/-1.2 kg/m(2). MEASUREMENTS: Body composition was assessed by dual energy X-ray absorptiometry and computerized tomography. Fasting insulin, glucose and leptin levels, and the homeostasis model assessment of insulin sensitivity (HOMA-IR) were assessed. RESULTS: The girls had significantly lower glucose levels than the boys. The ethnic group differences (African American children vs white children) in fat mass, total CT fat, subcutaneous CT fat, insulin level, leptin level, and higher HOMA-IR were not significant after adjusting for age or pubertal stage. These differences in abdominal fat and subcutaneous abdominal fat were also not independent of total body fat or BMI. No ethnic group differences in visceral abdominal fat were noted. Insulin level and HOMA IR were associated with leptin level (independent of fat mass) and fat mass. Leptin level was associated with fat mass, total CT fat, and subcutaneous CT fat; however the associations between the CT fat measures and leptin were not independent of total body fat mass. CONCLUSIONS: Neither visceral abdominal fat, subcutaneous abdominal fat, insulin levels, or insulin resistance differed by ethnic group when adjusted for age or pubertal status. This contrasts with findings in adults and non-obese children which suggest lower levels of visceral fat and higher insulin levels and insulin resistance in African American children and adolescents.

Prevalence and risk factors for overweight and obesity in children from Seychelles, a country in rapid transition: the importance of early growth.

OBJECTIVES: To establish the prevalence of overweight and obesity and related risk factors in children from Seychelles (Indian Ocean), a country in rapid economic and epidemiological transition. DESIGN: Cross-sectional study with retrospective access to early life data. SUBJECTS: All children from all schools of Seychelles, in four selected school grades (kindergarten, fourth, seventh and tenth year of obligatory school) in 1999. A total of 5514 children aged 4.5-17.4 y were measured, corresponding to 83.5% of the eligible population. MEASUREMENTS: Overweight and obesity, using age- and sex-specific body mass index (BMI) cut-off points as defined by the International Obesity Task Force. RESULTS: Some 12.6% (95% confidence interval: 11.8-13.5%) of the children were overweight and 3.8% (3.3-4.4%) were obese. Weight gain (kg) during the first year of life was strongly associated with subsequent overweight (odds ratio 1.46, 95% confidence interval 1.27-1.67) and obesity (1.59, 1.29-1.97) in childhood, independently of birth weight. Increased maternal BMI (kg/m(2)) was also associated with overweight (1.07, 1.03-1.10) and obesity (1.09, 1.04-1.14) in the offspring. CONCLUSION: Prevalence of overweight and obesity among school children in Seychelles was as high as or higher than in some industrialized countries. If confirmed in other environments, the strong association between weight gain during the first year of life and subsequent obesity in childhood could affect the way optimal infant weight gain is defined in countries where public health priorities are changing.

Energy expenditure and intake in children with sickle cell disease during acute illness.

BACKGROUND: Children with sickle cell disease have frequent bouts of pain and infection which may increase energy expenditure, decrease energy intake and lead to a subsequent energy deficit. METHODS: Two groups of African-American children with sickle cell disease-SS genotype were enrolled in this study upon hospital admission for a sickle cell disease related illness: a younger (<6 years, n=14, 7 M) and older group (> or =6 years, n=17, 8 M). Body composition and dietary intake were assessed, and sleeping (younger) or resting energy expenditure (older) were measured by indirect calorimetry at admission and one month later at steady state. RESULTS: Energy expenditure was not different between the two timepoints for younger children, but was slightly elevated at steady state (+50 kcal/d, P=0.049) in the older group. After controlling for gender, changes in fat-free mass and dietary intake, the significance disappeared. Energy intake in both groups was significantly depressed at admission compared to follow-up (P<0.01). CONCLUSIONS: These children and adolescents did not expend excess energy during their acute illness, however, an energy deficit was observed secondary to poor energy intake. Since 20% of patients with sickle cell disease have multiple hospitalizations per year, these results provide justification for the development and evaluation of nutrition care protocols to maintain adequate caloric intake during hospitalization and recovery.

Red blood cell folate and serum vitamin B12 status in children with sickle cell disease.

PURPOSE: To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters. PATIENTS AND METHODS: Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years. RESULTS: Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P < 0.01) decreased with increasing age. CONCLUSIONS: More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.